Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of RANKL/OPG mRNA Expression in Marrow Stromal Cells.
10.3346/jkms.2001.16.6.769
- Author:
Hoyeon CHUNG
1
;
Young Soon KANG
;
Chang Sun HWANG
;
In Kul MOON
;
Chang Hoon YIM
;
Kyu Hong CHOI
;
Ki Ok HAN
;
Hak Chul JANG
;
Hyun Koo YOON
;
In Kwon HAN
Author Information
1. Department of Medicine/Endocrinology, Laboratory of Endocrinology, Sungkyunkwan University School of Medicine, Samsung Cheil Hospital, Seoul, Korea. chy1009@samsung.co.kr
- Publication Type:Original Article
- Keywords:
Glucocorticoids;
Osteoclasts;
OPG;
RANKL
- MeSH:
Animal;
Bone Marrow Cells/*cytology;
Calcitriol/pharmacology;
Calcium Channel Agonists/pharmacology;
Carrier Proteins/*genetics;
Cell Differentiation/drug effects;
Cells, Cultured;
Dexamethasone/pharmacology;
Gene Expression/drug effects;
Glucocorticoids, Synthetic/pharmacology;
Glycoproteins/*genetics;
Immunosuppressive Agents/*pharmacology;
Male;
Membrane Glycoproteins/*genetics;
Mice;
Mice, Inbred ICR;
Osteoclasts/*cytology;
Pregnenediones/*pharmacology;
RNA, Messenger/analysis;
Receptors, Cytoplasmic and Nuclear/*genetics;
Stromal Cells/cytology
- From:Journal of Korean Medical Science
2001;16(6):769-773
- CountryRepublic of Korea
- Language:English
-
Abstract:
Information on precise effects of deflazacort on bone cell function, especially osteoclasts, is quite limited. Therefore, the present study was undertaken to test effects of deflazacort on osteoclast-like cell formation in mouse bone marrow cultures and on the regulation of osteoprotegerin (OPG) and its ligand (RANKL) mRNA expressions by RT-PCR in the ST2 marrow stromal cells. TRAP-positive mononuclear cells increased after the treatment of deflazacort at 10(-9) to 10(-7) M alone for 6 days in a dose-dependent manner. Number of TRAP-positive multi-nucleated cells (MNCs) increased significantly with combined treatment of deflazacort at 10(-7) M and 1,25-(OH)2D3 at 10(-9) M compared to that of cultures treated with 1,25-(OH)2D3 alone (p<0.05). Exposure to deflazacort at 10(-7) M in the presence of 1,25-(OH)2D3 at 10(-9) M in the last 3-day culture had greater stimulatory effect on osteoclast-like cell formation than that of the first 3-day culture did. Deflazacort at 10(-10) -10(-6) M downregulated OPG and upregulated RANKL in mRNA levels in a dose-dependent manner. These observations suggest that deflazacort stimulate osteoclast precursor in the absence of 1,25-(OH)2D3 and enhance differentiation of osteoclasts in the presence of 1,25-(OH)2D3. These effects are, in part, thought to be mediated by the regulation of the expression of OPG and RANKL mRNA in marrow stromal cells.
